Studies will be undertaken to provide additional insight into the mechanism of action of thyroid hormones at the cellular level. The relationship of nuclear occupancy and response will be quantitated under various physiologic and pathologic settings. Although such studies will be carried out largely in the rat, appropriate correlative studies will be carried out in man whenever feasible. Efforts will be made at futher purification and characterization of the receptor sites and at characterization and quantitation of the nature of the mRNA stimulated by T3. Special attention will be directed to defining the molecular events which are responsible for the T3-dependent maturation of the central nervous system.